CD8 positive cytotoxic T lymphocytes (CTLs) have been shown to recognize epitope peptides derived from tumor-associated antigens (TAAs) on the major histocompatibility complex (MHC) class I molecule, and then kill the tumor cells. Since the discovery of the melanoma antigen (MAGE) family as the first example of TAAs, many other TAAs have been discovered through immunological approaches (NPL 1, 2), and some of the TAAs are now in the process of clinical development as immunotherapeutic targets.
Favorable TAAs are indispensable for the proliferation and survival of cancer cells. The use of such TAAs as targets for immunotherapy may minimize the well-described risk of immune escape of cancer cells attributable to deletion, mutation, and/or down-regulation of TAAs as a consequence of therapeutically driven immune selection. Accordingly, the identification of new TAAs capable of inducing potent and specific anti-tumor immune responses warrants further development. Thus, clinical application of peptide vaccination strategies in various types of cancer is ongoing (NPL 3-10). To date, there have been several reports of clinical trials using these TAAs-derived peptides. Unfortunately, so far, these cancer vaccine trials have yielded only a low objective response rate (NPL 11-13). Accordingly, there remains a need in the art for new TAAs suitable for use as immunotherapeutic targets.
TOPK (T-LAK cell-originated protein kinase) is a serine/threonine kinase that is member of the MAPK kinase (MAPKK) 3/6-related MAPKK family. This kinase phosphorylates p38 MAPK and participate in the regulation of cell cycle check point (NPL 14, 15). Gene expression analysis of TOPK using clinical samples indicated that TOPK is overexpressed in some malignant cancer, such as breast cancer, cholangio-carcinoma, hepatocellular carcinoma, leukemia, colorectal cancer and melanoma (NPL 16-19). Recent studies indicating that kinase activity plays an important role in breast carcinogenesis has renewed research interest in cancer-linked kinases such as TOPK. To that end, Northern blot analysis has revealed that TOPK transcript is highly expressed in breast cancer cells but is hardly detectable in normal human tissues except testis. In addition, knockdown of endogenous TOPK expression by siRNA in breast cancer cell lines has been shown to attenuate the cytokinesis and lead to apoptosis of the cancer cells (NPL 20).